Implantable medical devices increasingly incorporate drugs to improve the performance of the medical device or reduce side effects associated with implantation of the device. Sterilization processes suitable for medical devices that do not incorporate drugs may not be suitable for such devices that incorporate drugs, due to incompatibilities of the sterilization process and the drugs. Examples of sterilization processes include steam sterilization (e.g., autoclaving), chemical sterilization (e.g., ethylene oxide or vaporized hydrogen peroxide), and sterilization via radiation (e.g., gamma or e-beam). Steam sterilization may not be compatible with drugs that degrade under high temperature or humidity conditions. Chemical sterilization may not be compatible with drugs that have chemical groups that react with the sterilization chemical, such as ethylene oxide. Radiation typically alters the chemical structures of drugs incorporated into medical devices. Accordingly, some drugs may be incompatible with radiation sterilization and may be more or less sensitive to gamma versus e-beam radiation, depending on the nature of the specific drug.
With regard to radiation sterilization, gamma radiation is capable of penetrating much further into a product or packaging than e-beam radiation because gamma radiation is higher energy radiation than e-beam. As such, gamma radiation may be preferred to e-beam in certain situations where the product is thick or dense and sterility throughout must be demonstrated. However, due to the set up of typical sterilization facilities, products sterilized by gamma radiation may be over sterilized or exposed to gamma radiation for a longer time than is needed to achieve sufficient sterilization. On the other hand, facilities for e-beam sterilization are typically more capable of limiting exposure of a product to the amount of radiation energy necessary to achieve sufficient sterilization. Accordingly, e-beam sterilization can be gentler than gamma radiation to products and their packaging. Regardless of the sterilization process employed, the compatibility of a drug or device with a particular sterilization process should be drug or device dependent if the sterilization level of the process is roughly equivalent.
The compatibility of a drug with a sterilization process is likely to vary from drug or device to drug or device and sterilization process to sterilization process. As such, selection of a sterilization process for a device incorporating a drug should be carefully considered. For example minocycline, an antibiotic commonly employed in medical devices to reduce infection associated with use or implantation of the devices, degrades to unacceptable levels under steam sterilization, but does not appear to substantially degrade with ethylene oxide sterilization. Rifampin, another antimicrobial agent that is employed in currently available implantable medical devices, is often used in combination with minocycline in medical devices to further reduce the risk of infection. Many of these rifampin-containing implantable medical devices are sterilized via treatment with ethylene oxide and numerous studies have reported no detectable degradation or no loss in antimicrobial activity when devices containing rifampin are treated with ethylene oxide.
Sterilization procedures for medical devices should be carefully selected, especially in devices that incorporate drugs. If a device incorporates more than one drug, the selection of a sterilization process can be more difficult if the drugs are incompatible with different sterilization processes. There is a need for implantable medical devices incorporating multiple drugs, which devices are produced with sterilization incompatibilities of the drugs in mind.